WO2001068034B1 - 1, 2, 4-triazoloribonucleoside prodrugs and their administration to treat viral disease conditions - Google Patents

1, 2, 4-triazoloribonucleoside prodrugs and their administration to treat viral disease conditions

Info

Publication number
WO2001068034B1
WO2001068034B1 PCT/US2001/008769 US0108769W WO0168034B1 WO 2001068034 B1 WO2001068034 B1 WO 2001068034B1 US 0108769 W US0108769 W US 0108769W WO 0168034 B1 WO0168034 B1 WO 0168034B1
Authority
WO
WIPO (PCT)
Prior art keywords
group
compound
compound according
masking
alkynyl
Prior art date
Application number
PCT/US2001/008769
Other languages
French (fr)
Other versions
WO2001068034A3 (en
WO2001068034A2 (en
Inventor
Guangyi Wang
Kanda Ramasamy
Johnson Lau
Original Assignee
Icn Pharmaceuticals
Guangyi Wang
Kanda Ramasamy
Johnson Lau
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to AU50881/01A priority Critical patent/AU5088101A/en
Application filed by Icn Pharmaceuticals, Guangyi Wang, Kanda Ramasamy, Johnson Lau filed Critical Icn Pharmaceuticals
Priority to EP01924208A priority patent/EP1207890A4/en
Priority to SK1152-2002A priority patent/SK11522002A3/en
Priority to BRPI0109143-3A priority patent/BR0109143A/en
Priority to JP2001566501A priority patent/JP2003530322A/en
Priority to HU0302334A priority patent/HUP0302334A2/en
Priority to CA002400043A priority patent/CA2400043A1/en
Priority to MXPA02008608A priority patent/MXPA02008608A/en
Publication of WO2001068034A2 publication Critical patent/WO2001068034A2/en
Publication of WO2001068034A3 publication Critical patent/WO2001068034A3/en
Publication of WO2001068034B1 publication Critical patent/WO2001068034B1/en
Priority to IL151073A priority patent/IL151073A0/en
Priority to NO20024385A priority patent/NO20024385L/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/14—Pyrrolo-pyrimidine radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/052—Imidazole radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/056—Triazole or tetrazole radicals

Abstract

Prodrug forms of Levovirin include bio-reversible modifications on the sugar moiety and/or bio-reversible modifications on the triazole moiety. Contemplated prodrug forms may be used in pharmaceutical compositions, which may be used to treat an infection, an infestation, a neoplasm, or an autoimmune disease. Further contemplated uses include immunomodulation, and particularly modulation of Type 1 and Type 2 cytokine expression.

Claims

AMENDED CLAIMS[received by the International Bureau on 18 January 2002 ( 18.01.02); original claims 1, 7, 10. 13, 16 and 18 amended; remaining claims unchanged (4 pages)]
1. A compound according to formula (I)
Figure imgf000002_0001
wherein Ri is a masking group of the amino group; wherein R is H, an amino acid radical, -C(O)R, or -P(O)(OR')2, wherein R is Cι-C,7 alkyl, alkenyl, or alkynyl, and R' is a masking group of the phosphate group; R3 and R3' are independently H or C1-C18 acyl; and wherein Ri and R2 are not hydrogen at the same time.
2. The compound of claim 1 wherein Ri is selected from the group consisting of acetyloxypentanoic acid, para-acetyloxybenzyloxycarbonyl, para- acetyldisulfidecarbonyl; and wherein R2, R3 and R3' are independently H or acetyl.
3. The compound of claim 2 wherein R3 and R3' are H.
4. The compound of claim 2 wherein R2 is hydrogen.
5. The compound of claim 2 wherein Ri is a masking group comprising a carbonyl function.
6. The compound of claim 1 wherein R3 and R3' are hydrogen, and wherein R2 comprises a phosphate.
7. A compound according to formula (II)
Figure imgf000002_0002
39 wherein Ri is a masking group of the amino group having a structure selected from the group consisting of o II o II
R-C-O— (CH2)4-C — ,
O , , O
R-c 11 -x — / (J/ \ — CH2-0— C " —
o II o II
R-C— S— (CH2)2-0-C — o
II R— S— S— C —
0 II R— S— S— (CH2)2-0-C —
O II R— C— X— CH2— ; and wherein X is O or S, and R is a Cι-Cι8 alkyl, alkenyl, alkynyl, aryl, or aralkyl.
8. The compound of claim 7 wherein the masking group comprises a disulfide bond.
9. The compound of claim 7 wherein the masking group is selected from the group consisting of
o o
II II
R— C— O— (CH2)4-C —
O o
II II
R-C-X- // -CH2-0-C- , and
O o
II II
R-C-S— (CH2)2-0-C— ; and
wherein X is O or S, and R is a Cι-Cι8 alkyl, alkenyl, alkynyl, aryl, or aralkyl.
10. A compound according to formula (III)
Figure imgf000003_0001
40 wherein Ri is H or a masking group of the amino group, and wherein R and R ' are independently a masking group of the phosphate group having a structure selected from the group consisting of o ,-----,
R— C— X — (, > — CH2— R— S— S— (CH2)2— _
R_S_S→ ^CH ~ , R-C-X-CH2- ; and wherein X is O or S, and R is C]-Cι8 alkyl, alkenyl, alkynyl, aryl, or aralkyl.
11. The compound of claim 10 wherein Rj is a masking group.
12. The compound of claim 10 wherein R is a masking group comprising a disulfide bond.
13. A compound according to formula (IN)
Figure imgf000004_0001
wherein Ri is H or a masking group of the amino group, and wherein R is a group having a structure selected from the group consisting of o o o
II II I I
R-C-S— (CH2)2-0-P— f R_o-P—
R-C— S— (CH2)2— O R-o
0
Figure imgf000004_0002
O
NH I M-CH I
O O-M wherein R is C]-Cι8 alkyl, alkenyl, alkynyl, aryl, or aralkyl, and wherein M is alkyl, alkenyl, alkynyl, aralkyl, aryl, or a hydrophobic group.
14. The compound of claim 13 wherein the hydrophobic group is selected from the group consisting of a cholic acid, a bile acid, a cholesterol derivative and a vitamin D derivative.
15. The compound of claim 14 wherein R comprises a phosphate.
16. A method of treating a mammal having a viral infection comprising: providing a pharmaceutical composition that includes a compound selected from the group consisting of a compound according to claim 1 , a compound according to claim 7 a compound according to claim 10, and a compound according to claim 13; and administering the pharmaceutical composition to the mammal.
17. The method of claim 16 wherein the viral infection comprises an infection with an HCV virus or an HBV virus, and wherein the mammal is a human.
18. A method of modulating a lymphokine profile in a mammal comprising: providing a pharmaceutical composition that includes a compound selected from the group consisting of a compound according to claim 1, a compound according to claim 7 a compound according to claim 10, and a compound according to claim 13; and administering the pharmaceutical composition to the mammal in a dosage effective to reduce expression of a type 1 cytokine and stimulate expression of a Type 2 cytokine.
19. The method of claim 18 wherein the mammal is a human.
42
PCT/US2001/008769 2000-03-15 2001-03-15 1, 2, 4-triazoloribonucleoside prodrugs and their administration to treat viral disease conditions WO2001068034A2 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
HU0302334A HUP0302334A2 (en) 2000-03-15 2001-03-15 Antiviral prodrugs
EP01924208A EP1207890A4 (en) 2000-03-15 2001-03-15 Antiviral prodrugs
SK1152-2002A SK11522002A3 (en) 2000-03-15 2001-03-15 1,2,4-triazoloribonucleoside prodrugs and their administration to treat viral disease conditions
BRPI0109143-3A BR0109143A (en) 2000-03-15 2001-03-15 antiviral prodrugs
JP2001566501A JP2003530322A (en) 2000-03-15 2001-03-15 Antiviral prodrug
AU50881/01A AU5088101A (en) 2000-03-15 2001-03-15 Antiviral prodrugs
CA002400043A CA2400043A1 (en) 2000-03-15 2001-03-15 Antiviral prodrugs
MXPA02008608A MXPA02008608A (en) 2000-03-15 2001-03-15 Antiviral prodrugs.
IL151073A IL151073A0 (en) 2000-03-15 2002-08-05 Antiviral prodrugs
NO20024385A NO20024385L (en) 2000-03-15 2002-09-13 Antiviral pro-drugs

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US18967200P 2000-03-15 2000-03-15
US60/189,672 2000-03-15
US09/594,410 2000-06-16
US09/594,410 US6495677B1 (en) 2000-02-15 2000-06-16 Nucleoside compounds

Publications (3)

Publication Number Publication Date
WO2001068034A2 WO2001068034A2 (en) 2001-09-20
WO2001068034A3 WO2001068034A3 (en) 2002-03-21
WO2001068034B1 true WO2001068034B1 (en) 2002-05-10

Family

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PCT/US2001/008713 WO2001068663A1 (en) 2000-03-15 2001-03-15 Nucleoside compounds and uses thereof

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Country Status (18)

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US (1) US6495677B1 (en)
EP (2) EP1207890A4 (en)
JP (2) JP2004505889A (en)
KR (2) KR20030062227A (en)
CN (2) CN1416431A (en)
AU (2) AU4755601A (en)
BR (2) BR0109144A (en)
CA (2) CA2400370A1 (en)
CZ (2) CZ20023119A3 (en)
DE (1) DE20121305U1 (en)
HU (2) HUP0301730A2 (en)
IL (1) IL151073A0 (en)
MX (2) MXPA02008608A (en)
NO (2) NO20024355L (en)
PL (2) PL365985A1 (en)
RU (2) RU2002121631A (en)
SK (2) SK11502002A3 (en)
WO (2) WO2001068034A2 (en)

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